HIV status in discordant couples in sub-Saharan Africa: a systematic review and meta-analysis

Eyawo, Oghenowede; Walque, Damien de; Ford, Nathan; Gakii, Gloria; Lester, Richard; Mills, Edward J.

doi:10.1016/s1473-3099(10)70189-4

Cited by 148 publications

(115 citation statements)

References 55 publications

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“…In the absence of a preventative vaccine, effective prophylactic biomedical technologies are urgently required. Campaigns aimed at encouraging monogamy and condom use have had limited success in areas where marriage has been identified as the major risk factor for HIV acquisition in women (3,15,16,21,25).Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2), the serotype most commonly associated with genital herpes, are responsible for two intersecting epidemics, where the disease caused by one virus facilitates the transmission of and pathogenesis by the other. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV-1 acquisition (33,34,43).…”

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confidence: 99%

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Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ؎ 335 g day ؊1 (ACV) and 321 ؎ 207 g day ؊1 (TFV); sheep, 174 ؎ 14 g day ؊1 (ACV) and 185 ؎ 34 g day ؊1 (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ؎ 7.31 g ml ؊1 (ACV) and 20.6 ؎ 16.2 g ml ؊1 (TFV); cervicovaginal lavage fluid, 118 ؎ 113 ng ml ؊1 (ACV) and 191 ؎ 125 ng ml ؊1 (TFV); tissue, 173 ng g ؊1 (ACV) and 93 ng g ؊1 (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens. Significant progress has been achieved in providing increased access to HIV/AIDS services in several low-and middleincome countries (44). Despite these encouraging findings, women in the developing world remain disproportionately at risk of HIV infection. Seventy-six percent of new HIV infections in sub-Saharan Africa occur in women aged 15 to 24 years (42). The proportion is as high as 90% in South Africa (38). In the absence of a preventative vaccine, effective prophylactic biomedical technologies are urgently required. Campaigns aimed at encouraging monogamy and condom use have had limited success in areas where marriage has been identified as the major risk factor for HIV acquisition in women (3,15,16,21,25).Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2), the serotype most commonly associated with genital herpes, are responsible for two intersecting epidemics, where the disease caused by one virus facilitates the transmission of and pathogenesis by the other. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV-1 acquisition (33,34,43). A meta-analysis found that prevalent HSV-2 infection is associated with a threefold-increased risk of HIV acquisition among both men and women. These results suggest that, in areas of high HSV-2 prevalence, a substantial proportion of HIV infection is linked to HSV-2 infection (...

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confidence: 99%

mentioning

confidence: 99%

Simultaneous Delivery of Tenofovir and Acyclovir via an Intravaginal Ring

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…The global incidence of HIV was estimated at 2.6 million in 2009, and 22 million more people are predicted to acquire HIV by 2031 (16,42). Campaigns aimed at encouraging monogamy and condom use have had limited success in areas where marriage has been identified as the major risk factor for HIV acquisition in women (2,7,9,14,26). For decades, all attempts to develop a preexposure prophylaxis (PrEP) strategy for the prevention of HIV transmission have failed (5,42).…”

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confidence: 99%

Safety and Pharmacokinetics of Intravaginal Rings Delivering Tenofovir in Pig-Tailed Macaques

Moss

Malone

Smith

et al. 2012

Antimicrob Agents Chemother

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Antiretroviral-based microbicides applied topically to the vagina may play an important role in protecting women from HIV infection. Incorporation of the nucleoside reverse transcriptase inhibitor tenofovir (TFV) into intravaginal rings (IVRs) for sustained mucosal delivery may lead to increased microbicide product adherence and efficacy compared with those of conventional vaginal formulations. Formulations of a novel "pod IVR" platform spanning a range of IVR drug loadings and daily release rates of TFV were evaluated in a pig-tailed macaque model. The rings were safe and exhibited sustained release at controlled rates over 28 days. Vaginal secretion TFV levels were independent of IVR drug loading and were able to be varied over 1.5 log units by changing the ring configuration. Mean TFV levels in vaginal secretions were 72.4 ؎ 109 g ml ؊1 (slow releasing) and 1.84 ؎ 1.97 mg ml ؊1 (fast releasing). The mean TFV vaginal tissue concentration from the slow-releasing IVRs was 76.4 ؎ 54.8 g g ؊1 and remained at steady state 7 days after IVR removal, consistent with the long intracellular half-life of TFV. Intracellular tenofovir diphosphate (TFV-DP), the active moiety in defining efficacy, was measured in vaginal lymphocytes collected in the study using the fast-releasing IVR formulation. Mean intracellular TFV-DP levels of 446 ؎ 150 fmol/10 6 cells fall within a range that may be protective of simian-human immunodeficiency virus strain SF162p3 (SHIV SF162p3 ) infection in nonhuman primates. These data suggest that TFV-releasing IVRs based on the pod design have potential for the prevention of transmission of human immunodeficiency virus type 1 (HIV-1) and merit further clinical investigation.

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“…In most sub-Saharan African countries with generalized HIV epidemics, three-quarters of adults ages 20-49 years report being in cohabiting relationships [7][8][9]. Among people with HIV who are in stable relationships, up to half have an HIV-negative partner-that is, they are in a serodiscordant relationship (one partner is HIV-positive, the other is HIV-negative) [4].…”

Section: Statement Of the Problemmentioning

confidence: 99%

“…Data from 27 cohorts totaling 13, 061 sero-discordant couples in sub-Saharan Africa and Demographic and Health Survey (DHS) data on 1,145 serodiscordant couples in 14 countries indicated that the proportion of HIV-positive women in stable heterosexual sero-discordant relationships was 47% [7]. Population surveys in 2007-2008 in low-and middle-income countries revealed thatknowledge of HIV status is still low among people with HIV, with a median of 40% in 10countries [13].…”

Section: Literature Reviewmentioning

confidence: 99%